Levels of Alpha-L-fucosidase in serum of ostensibly healthy individuals are genetically determined. The mechanism controlling levels of the enzyme in serum is unknown. As an experimental tool to investigate this problem, lymphoid cell cultures derived from individuals who have inherited either high or low activity of Alpha-L-fucosidase in serum will be established. With these cell lines, the following questions will be asked: 1) Are there differences in the relative rates of synthesis of the polypeptide and carbohydrate chains of Alpha-L-fucosidase? 2) Are there differences in the processing the polypeptide and/or carbohydrate moieties of Alpha-L-fucosidase? 3) Are there differences in the sorting of Alpha-L-fucosidase into intracellular and extraccellular compartments? 4) Are there differences in Alpha-L-fucosidase m-RNA activity? Answers to these questions will provide novel information concerning the biosynthesis and processing of Alpha-L-fucosidase and will contribute to an understanding of the mechanism determining levels of Alpha-L-fucosidase in serum. This knowledge, besides being scientifically important, may also have clinical significance. The inheritance of decreased activity of Alpha-L-fucosidae in serum of females has been associated with increased risk for developing ovarian cancer. Thus, an understanding of the mechanism controlling levels of Alpha-L-fucosidase in serum may provide information concerning the etiology of ovarian cancer and the genetic factors involved in disease susceptibility. Moreover, alterations of Alpha-L-fucosidase have been associated with other severe diseases. These include fucosidosis, I-cell disease, cystic fibrosis, gastric cancer, diabetes mellitus, hepatic cirrhosis, acute viral hepatitis, Graves disease, various muscular diseases and acute and chronic lymphoblastic leukemia. Thus, the proposed investigations may be relevant for an improved understanding of the molecular pathology of these diseases.